Project Summary This F32 application proposes mentorship and training opportunities in three areas: 1) chronic pain clinical trials research, 2) systematic measurement of pain pathophysiology, and 3) mechanisms underlying motivation and adherence. Learned skills will be applied to conduct a research project that will examine whether a brain system involved in motivated behavior (i.e., mesocorticolimbic system) is associated with treatment motivation and adherence to Cognitive Behavioral Therapy (CBT) in chronic pain patients. Treatment adherence is an imperative factor for successful chronic pain management. However, nonadherence is a critical public health concern that renders effective symptom management challenging. Well-established frameworks describe motivation as the cornerstone of adherence to lifestyle modifications commonly instructed through CBT. Examples of these modifications include pacing pain-exacerbating activities, engaging in relaxation exercises, and challenging catastrophic thoughts about pain. Psychosocial constructs influencing individuals? motivation for treatment are proposed within these frameworks; however, potential neurobiological factors underlying these constructs have not been examined. The mesocorticolimbic system is an ideal candidate mechanism of treatment-related motivation in individuals with chronic pain, given its association with motivated behavior and aberrant function in chronic pain. This project will be embedded into an NIH-funded parent R01 that examines whether adults with sickle cell disease (SCD) who report chronic pain and sleep disturbance experience clinical pain reduction following CBT for insomnia (CBTi). The proposed project?s aims are distinct from the parent study, given this study?s focus on neural mechanisms of treatment motivation and adherence. Before treatment, participants will complete questionnaires and undergo structural and functional neuroimaging. The latter will include a 10-minute resting-state scan, which is a paradigm designed to measure intrinsic functional connectivity (FC), or correlated activity among brain regions over time. Intrinsic FC has been described as a robust approach to measure neural network integrity, providing key information about disease states. Study participation is approximately 9 weeks and participants complete 5 CBTi sessions during this time. The sum of CBTi session attendance, daily symptom diary completion, and practice of assigned therapy homework will be used to determine adherence. Analyses will be completed on questionnaire and neuroimaging data from 27 adults with SCD to 1) determine whether pre-CBTi mesocorticolimbic functioning is associated with treatment- related motivation, and 2) assess whether treatment-related motivation moderates the relationship between pre-CBTi mesocorticolimbic FC and adherence to CBTi. Findings will further our knowledge about mechanisms of treatment adherence in chronic pain and help identify potential therapeutic targets to improve motivation, which will ultimately help patients more effectively engage in existing and novel treatments.